Submissions for variant NM_004714.3(DYRK1B):c.1748C>T (p.Ala583Val)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
New York Genome Center	RCV003336607	SCV004046639	uncertain significance	Abdominal obesity-metabolic syndrome 3	2023-01-06	criteria provided, single submitter	clinical testing	The c.1748C>T, p.(Ala583Val) missense variant identified in the DYRK1B gene has not been reported in affected individuals in theliterature. The variant is observed in 33 out of ~569,000 heterozygous alleles (no homozygotes) in population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze8), suggesting it is not a common benign variant in the populations represented in those databases. The c.1748C>T variant is located in the last exon of this 11-exongene and is predicted to replace a moderately conserved alanine amino acid with valine at position 583 of the encoded protein. In silico predictions are not in favorof the variant’s damaging effect [REVEL = 0.058]; however, functional studies to support or refute these predictions have not been reported. Due to the lack of compelling evidence for its pathogenicity, the c.1748C>T, p.(Ala583Val) missense variant identified in the DYRK1B gene is reported as a Variant of Uncertain Significance.
PreventionGenetics, part of Exact Sciences	RCV004747288	SCV005350531	likely benign	DYRK1B-related disorder	2024-03-27	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).